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Genetic counseling: Down Syndrome - Trisomy 21-2
Down Syndrome - Trisomy 21 Genetics *3 possible etiologies: **Full trisomy 21 (95% of the cases) ***Due to nondisjunction during meiosis ***Usually maternal nondisjunction (90-95% of these cases) *75% of maternal nondisjunction occurs during meiosis 1 ***1% recurrence risk, unless the mother's age related risk is higher than 1%, in which case the age-related risk is quoted **Unbalanced translocation (3-4% of cases) ***50% of cases a parent carries a balanced translocation ***50% of the unbalanced translocations are de novo and occur during fertilization ***Recurrence risk is 100% for a parental 21:21 translocation ***For a 21:14 translocation, recurrence is 16% if in the mother and 5% if in the father **Mosaicism (1-2% of cases) ***Due to nondisjunction during mitosis, early in embryonic development ***Only cells that descend from that specific cell where nondisjunction occurred will be trisomy 21 ***Usually associated with a less severe phenotype *Molecular Genetics **Ongoing effort to define Chromosome 21 critical region **Narrowed to 21q22 **DSCR1 is a candidate gene suspected to be involved in the pathogenesis of DS Incidence *One in every 650-1,000 children is born with down syndrome Clinical Features *Intelligence **Mild to moderate mental retardation seen in most individuals (ranges from ~40-80) **Language delays *Cardiac **>40% are born with congenital heart defects ***Av canal and VSD are common *Gastrointestinal **Duodenal atresia is the most common **Duodenal web (partial obstruction) **Tracheoesophageal fistula **Pyloric stenosis **Omphalocele **Hirschprung's disease **Imperforate anus **Annular pancreas **Celiac disease **Associations with vomiting, diarrhea, constipation, and feeding difficulties may be associated *Auditory **Recurrent otitis media **Some degree of hearing loss is present in ~90% of patients **Conductive hearing loss due to fluid accumulation **Sensorineural hearing loss is also seen *Craniofacial **Macroglossia (60%) ***May cause feeding difficulty **Dental malocclusions (100%) **Constellation of characteristic facial features ***Brachycephaly ***Low nasal root, flat nasal bridge ***Epicanthic folds ***Small and occasionally overfolded ears ***Short neck sometime seen with redundant skin at the nape ***Brushfield spots *Skeletal **14% have increased mobility of the cervical spine at the level of the 1st and 2nd vertebrae (atlantoaxial instability) *other **Respiratory problems can be due to midfacial hypoplasia which results in narrow airways ***Infections (recurrent croup due to narrow trachea) ***Obstructive airway disease ***Sleep apnea **Leukemia ***Risk of developing leukemia is 15-30 times higher in Down syndrome patients than in the general population **Hypothyroidism (15%) ***Common during adolescence ***Yearly monitoring of TSH and T(subscript)4 levels recommended **Alzheimer's Disease ***15% of adults with average age of onset ~50 yrs **Eye problems ***Strabismus ***cataracts **Seizures (5-10%) ***Correlation between age and prevalence ***Peaks at infancy and 4th-5th decade of life **Short stature (average at 3rd percentile) **Obesity **Wide gap between first and second toes **Hypotonia **Clinodactyly of the 5th fingers Natural History/Prognosis *Life expectancy has significantly increased **No congenital heart defects: >60 yrs old **Congenital heart defects: 30-35 yrs old *Causes of death **Leukemia (malignancy) **Infections Treatment and Management *Echocardiograms, EKG, chest X-rays to monitor heart defects **Surgery may be required *Ophthalmology exams *Hearing exams *Abdominal X-rays, barium swallow or enema to follow digestive problems *TSH levels to detect hypothyroidism *Early intervention for MR and developmental delays *Physical therapy for gross and fine motor skills *Speech therapy References *Jones KL (1997). Smith's Recognizable Patterns of Human Malformation. Philadelphia: W.B. Saunders Company *Jorde LB, Carey JC, Bamshad MJ, White RL (1999). Medical Genetics. 2nd ed. Philadelphia: Mosby. *Cohen WI (1999). Health Care Guidelines for Individuals with Down Syndrome: 1999 Revision (Down Syndrome Preventive Medical Check List). Down Syndrome Quarterly. *Web References: OMIM Entry #190685 Notes The information in this outline was last updated in 2000. This material has been imported fom the wikibook "Genetic counseling"[ http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License.